The proposed research continues to be directed toward acquiring a better understanding of the transfer of solutes and water across renal tubules with emphasis on the control mechanisms exerted by factors acting on the peritubular side of the epithelium, and on the tight junctions. Micropuncture, microperfusion and electrophysiological techniques will be used. Specifically, the nature of the effect of alterations in the composition of the peritubular fluid environment on transport functions of different nephron segments will be examined. The mechanism of the rise in distal tubular electrolyte permeability, resulting from the ADH-induced increase in late distal tubular osmolality will be studied. The effect of induced osmotic gradients on transport numbers of ions will be evaluated with electrophysiological techniques. The permeability of peritubular capillaries to protein will be estimated. The effect of electrical gradients across distal tubules on transport of calcium will be investigated to elucidate the hypocalciuric action of thiazide diuretics and finally, micropuncture methods will also be employed to test whether changes in bicarbonate concentration in peritubular fluid play a role in the production of natriuresis which occurs during acute hyperkalemia.